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Title: The relationship between the tumorigenicity-promoting function of C-FABP and its fatty acid-binding ability
Author: Bao, Zheng Zheng
ISNI:       0000 0004 2705 0120
Awarding Body: University of Liverpool
Current Institution: University of Liverpool
Date of Award: 2010
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To study the possible relationship between the tumorigenicity-promoting activity of cutaneous fatty acid binding protein (C-FABP) and its fatty acid-binding capability, mutations were generated on the fatty acid-binding motif of the C-FABP cDNA. The wild type and mutated C-FABP cDNAs were transfected respectively into the LNCaP prostate cancer cells, which do not express C-FABP prior to the transfection, to generate a clone expressing a wild type C-FABP which can bind to fatty acids; and two clones expressing mutated C-FABPs which are less capable of binding to fatty acids. The increased wild type C-FABP expression in LNCaP cells significantly increased cell proliferation, invasiveness, and tumorigenicity in vitro, whereas, the increased expression of both mutant forms of C-FABP did not significantly change these characteristics. When inoculated in nude mouse, 7 out of 8 mice produced tumors in the wild type group, with an average tumour weight of 342.9±144.8mg. In single mutant group, 4 out of 8 mice produced tumors with an average tumour weight of 217.5±69.5mg. Whereas in the double mutant and control group, only 3 out of 8 mice produced tumors with average sizes of 59.33±19.0mg and 46.7±15.3mg, respectively. The increased expression of wild type C-FABP, which is able to bind fatty acids, produced 4 more tumors and significantly increased the tumor size by 7.3- fold, comparing with the control. In contrast, increased expression of the mutant C-F ABP, which only has a similar ability of binding fatty acids to the control cells, produced the same number of tumours with similar sizes with those produced by the control cells. Our results suggest that the biological ability of C-FABP to promote tumourigenicity of the prostate cancer cells depends on its ability of binding to fatty acids. Thus C-FABP may facilitate cancer development through transporting fatty acids into cells.
Supervisor: Ke, Y. Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral